miR-Cabiner: A universal microRNA sensing platform based on self- stacking cascaded bicyclic DNA circuit-mediated CRISPR/Cas12a

Abstract Background CRISPR/Cas12a-based diagnostics enable great potential in the sensing nucleic acid, but its application was limited by the sequence dependence. Results A platform termed miR-Cabiner (a universal miRNA sensing platform based on self-stacking cascaded bicyclic DNA circuit-mediated CRISPR/Cas12a) is demonstrated that is sensitive and universal for analyzing miRNAs. This platform combines catalytic hairpin assembly (CHA) and hybrid chain reaction (HCR) into a unified circuit and finally cascaded to CRISPR/Cas12a. Compared to the CHA-Cas12a and HCR-Cas12a systems, miR-Cabiner exhibits a significantly higher reaction rate. Panels of miRNAs (miR-130a, miR-10b, miR-21, miR-1285), which are associated with diagnosis, staging, and prognosis of breast cancer were designed to demonstrate the universality of miR-Cabine. Four miRNAs can be detected to fm-level by simply tunning the sequence in CHA components. Additionally, miRNA panel analysis also shows high accuracy in practical sample. Conclusion This universally applicable platform for detecting miRNA may serve as an excellent tool for clinical diagnosis.